Tumoral markers detected by copy number variation analysis (aCGH) and large scale gene expression profiling in penile carcinomas

• Grant number: 11/03974-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2011
• End date: December 31, 2011
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Silvia Regina Rogatto
• Grantee: Ariane Fidelis Busso Lopes
• Host Institution: Hospital A C Camargo. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Penile cancer is a rare malignancy that occurs predominantly in men after the sixth decade of life. Molecular genetic data in penile cancer are extremely limited. This project was approved by FAPESP in Master degree (Process 2009/068511-7) and the thesis was presented to the Defense Counsel; however, the Committee members suggested, unanimously, the promotion to PhD. For the purpose of data publication, we need to confirm and validate the results and this is the reason why this project was designed. During the Master project, it was evaluated copy number variations and gene expression profiling by large-scale analysis in penile carcinomas in 4x44K platforms (Agilent) according to HPV genotype (Linear Array HPV Test Genotyping kit, Roche). HPV infection was reported to 32% of the tumors evaluated (10/31 cases). The aCGH data showed 450 copy number alterations including frequent gains in 3q, 8q, 9p, 9q and 22q and chromosomal losses in 3p, 4q, 8p, 10p, 10q, 19p, 21p, and Y. It was found a higher number of genomic imbalances in HPV- tumors in comparison to HPV+. In addition, gains on 19q13.32 were detected exclusively in HPV+ cases. More than 3,000 differentially expressed genes were found by oligoarrays analysis including central network molecules presented in cell cycle, immune modulation and matrix metalloproteinases. Two hundred seventy nine genes had differentially transcript expression for HPV+ in comparison to HPV- tumors mainly related to immune response and inflammation. Afterwards, genomic and transcriptomic data were submitted to integrated analysis and it was identified several molecular markers candidates in penile tumors. Based on the previous analysis, the aim of this project is to evaluate the expression of 13 genes and/or proteins (TNFSF10, FLI1, DLC1, LAMP3, PPARG, SBF1, MMP1, STAT1, DAXX, SPP1, IFIT2, PI3 e TNFSF13B) by qRT-PCR and imunohistochemistry, respectively. The goal of the study is to confirm the data of large scale experiments and, therewith, allow the identification of molecular markers and therapeutic targets that could result in the reduction of morbidity and mortality caused by this carcinoma. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BUSSO-LOPES, ARIANE F.; MARCHI, FABIO A.; KUASNE, HELLEN; SCAPULATEMPO-NETO, CRISTOVAM; TRINDADE-FILHO, JOSE CARLOS S.; DE JESUS, CARLOS MARCIO N.; LOPES, ADEMAR; GUIMARAES, GUSTAVO C.; ROGATTO, SILVIA R.. Genomic Profiling of Human Penile Carcinoma Predicts Worse Prognosis and Survival. Cancer Prevention Research, v. 8, n. 2, p. 149-156, FEB 2015. (09/06851-7, 09/52088-3, 10/51601-6, 11/03974-0)